title: MicroRNA-133b stimulates ovarian estradiol synthesis by targeting Foxl2.
abstract: Forkhead L2 (Foxl2) is expressed in ovarian granulosa cells and participates in steroidogenesis by transcriptionally regulating target genes such as steroidogenic acute regulatory protein (StAR) and CYP19A1. In this study, a direct link between microRNA-133b (miR-133b) and Foxl2-mediated estradiol release in granulosa cells was established. miR-133b was involved in follicle-stimulating hormone (FSH)-induced estrogen production. Luciferase assays confirmed that miR-133b was bound to the 3' untranslated region (3'UTR) of Foxl2 mRNA. Consistent with this finding, miR-133b overexpression reduced the Foxl2 levels. Furthermore, miR-133b inhibited Foxl2 binding to the StAR and CYP19A1 promoter sequences. These results demonstrate that miR-133b down-regulates Foxl2 expression in granulosa cells by directly targeting the 3'UTR, thus inhibiting the Foxl2-mediated transcriptional repression of StAR and CYP19A1to promote estradiol production.
authors.affiliation: Reproductive Medicine Center, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, PR China.
authors.forename: Anyi
authors.initials: A
authors.lastname: Dai
authors.forename: Haixiang
authors.initials: H
authors.lastname: Sun
authors.forename: Ting
authors.initials: T
authors.lastname: Fang
authors.forename: Qun
authors.initials: Q
authors.lastname: Zhang
authors.forename: Shaogen
authors.initials: S
authors.lastname: Wu
authors.forename: Yue
authors.initials: Y
authors.lastname: Jiang
authors.forename: Lijun
authors.initials: L
authors.lastname: Ding
authors.forename: Guijun
authors.initials: G
authors.lastname: Yan
authors.forename: Yali
authors.initials: Y
authors.lastname: Hu
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D017931:DNA Primers; D004958:Estradiol / Q000096:biosynthesis*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000502:physiology; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D035683:MicroRNAs / Q000502:physiology*; D010053:Ovary / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics; D011401:Promoter Regions, Genetic; D060888:Real-Time Polymerase Chain Reaction; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D020413:3' Untranslated Regions; D017931:DNA Primers; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors; C498893:Foxl2 protein, mouse; D035683:MicroRNAs; C517732:Mirn133 microRNA, mouse; D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein; D004958:Estradiol; D005640:Follicle Stimulating Hormone; D003577:Cytochrome P-450 Enzyme System
keywords: 3′ untranslated region; 3′UTR; ACVRIB; ACVRIIA; CREB; CYP; CYP19A1; ChIP; ERK; Estrogen; FSH; Foxl2; Granulosa cell; LH; MAPK; PI3K; PKA; POF; RBMS1; RNA binding motif, single stranded interacting protein 1; StAR; activin receptor typeIB; activin receptor typeIIA; adenosine-3′:5′-monophosphate; cAMP; cAMP response element binding protein; chromatin immunoprecipitation; cytochrome P450; extracellular regulated kinase; follicle-stimulating hormone; forkhead L2; luteinizing hormone; mGCs; miR-133b; microRNA-133b; mitogen-activated protein kinase; mouse granulosa cells; phosphoinositide 3-kinase; premature ovarian failure; protein kinase A; steroidogenic acute regulatory protein